Quality of Life in elderly patients with cancer

The incidence of most types of cancers is age-dependent and the progressive ageing is rapidly increasing the number of elderly people who need treatment for cancer. Elderly patients present peculiar characteristics that make the choice of the correct treatment more difficult and these patients are often undertreated. Moreover, elderly patients are largely underrepresented in cancer treatment trials, and this makes the experimental evidence on this topic even weaker. Health-related Quality of Life (QOL) has been considered as one of the hard end-points for clinical cancer research, and treatment of elderly cancer patients represents a typical situation where its assessment can be particularly useful, because the expected toxicity of treatment could be relevant in the discussion of the treatment choice. However, QOL assessment in the elderly is complicated by several unresolved methodological problems (higher frequency of illiteracy, worse compliance with the questionnaires, concomitant diseases, use of instruments not validated in the aged population). Conduct of clinical trials dedicated to elderly patients is now encouraged but there are few published studies. Advanced non-small-cell lung cancer is one of the fields with the largest amount of research on QOL in elderly patients. The ELVIS study demonstrated the efficacy of single-agent chemotherapy, both in terms of QOL and of survival. The MILES study, in which combination chemotherapy was not superior than single agents, showed that baseline QOL is a strong prognostic indicator in these patients. QOL of patients with breast cancer has been another important field in clinical research over the last decades, and interest on this topic in elderly patients is growing, from loco-regional to palliative treatment.     

MRC quality of life studies using a daily diary card—practical lessons learned from cancer trials

The UK Medical Research Council (MRC) Daily Diary Card for quality of life (QOL) assessment was first designed over ten years ago, and since then has been in continuous use in cancer clinical trials organized by the MRC Cancer Trials Office. However, clinical trials using this technique have only reached maturity since 1989 and later. Thus it is timely to review the experiences gained by use of this method of assessing QOL. Results from a series of clinical trials confirm that the Daily Diary Card appears to be a valid, reliable and sensitive instrument which is able to detect the transient changes in health and QOL which occur on a day to day basis during therapy for cancer. However, in early studies we also encountered a number of problems which were addressed during later MRC trials; we belleve that many of these are of general importance to any investigation of QOL in patients, many of the issues raised remain controversial, and the practical lessons learned from applying the Diary Card will be of relevance to those planning future studies of QOL assessment.     

A multistate Markov chain model for longitudinal, categorical quality-of-life data subject to non-ignorable missingness

Quality-of-life (QOL) is an important outcome in clinical research, particularly in cancer clinical trials. Typically, data are collected longitudinally from patients during treatment and subsequent follow-up. Missing data are a common problem, and missingness may arise in a non-ignorable fashion. In particular, the probability that a patient misses an assessment may depend on the patient's QOL at the time of the scheduled assessment. We propose a Markov chain model for the analysis of categorical outcomes derived from QOL measures. Our model assumes that transitions between QOL states depend on covariates through generalized logit models or proportional odds models. To account for non-ignorable missingness, we incorporate logistic regression models for the conditional probabilities of observing measurements, given their actual values. The model can accommodate time-dependent covariates. Estimation is by maximum likelihood, summing over all possible values of the missing measurements. We describe options for selecting parsimonious models, and we study the finite-sample properties of the estimators by simulation. We apply the techniques to data from a breast cancer clinical trial in which QOL assessments were made longitudinally, and in which missing data frequently arose.     

SUMMARY MEASURES AND STATISTICS FOR COMPARISON OF QUALITY OF LIFE IN A CLINICAL TRIAL OF CANCER THERAPY

Assessment of health related quality of life (QOL) has become an important endpoint in many clinical trials of cancer therapy. Most of these studies entail multiple QOL scales that are assessed repeatedly over time. As a result, the problem of multiple comparisons is a primary analytic challenge with these trials. The use of summary measures and statistics both reduces the number of hypotheses tested and facilitates the interpretation of trial results where the primary question is ‘Does the overall QOL differ between treatment arms?’ I present two classes of summary measures that are sensitive to consistent trends in the same direction across multiple assessment times or multiple QOL scales. Missing data strongly influences the choice between the two classes, where one class handles missing data on an individual basis, while the other class uses model-based strategies. I present the results from a clinical trial of adjuvant therapy for breast cancer that use summary measures with a focus on the practical issues that affect these analysis strategies, such as missing data and integration of QOL with efficacy endpoints such as survival. © 1997 by John Wiley & Sons, Ltd.     

Community Health Workers’ Support for Cancer Clinical Trials: Description and Explanation

Ethnic differences in participation in cancer clinical trials slow advances in medical knowledge that can reduce health care disparities. Community health workers (CHWs) are an increasingly important bridge between the health care system and underserved communities and could play an important role in increasing rates of clinical trial participation. We investigated community health workers’ orientations to medical research and cancer clinical trials with a mixed methods design: two focus groups, 11 intensive interviews, and a structured survey of 76 CHW training workshop participants. CHWs demonstrated high levels of commitment to improving the health of community members but considerable distrust of researchers’ motives, low levels of knowledge about cancer clinical trials, and frequent perceptions of bias in the health care system. Support for research is associated with more research experience, self-assessed knowledge, and Hispanic ethnicity, but with less seniority as a CHW. Neither actual knowledge of cancer clinical trials nor perceptions of bias in the health care system were related to degree of support for medical research. Community health workers perceive bias in the health care system but recognize the importance of medical research and are interested in learning more about cancer clinical trials. Research experience increases support for medical research; education increases perceptions of health care system bias.     

A semiparametric joint model for terminal trend of quality of life and survival in palliative care research

Palliative medicine is an interdisciplinary specialty focusing on improving quality of life (QOL) for patients with serious illness and their families. Palliative care programs are available or under development at over 80% of large US hospitals (300+ beds). Palliative care clinical trials present unique analytic challenges relative to evaluating the palliative care treatment efficacy which is to improve patients’ diminishing QOL as disease progresses towards end of life (EOL). A unique feature of palliative care clinical trials is that patients will experience decreasing QOL during the trial despite potentially beneficial treatment. Often longitudinal QOL and survival data are highly correlated which, in the face of censoring, makes it challenging to properly analyze and interpret terminal QOL trend. To address these issues, we propose a novel semiparametric statistical approach to jointly model the terminal trend of QOL and survival data. There are two sub‐models in our approach: a semiparametric mixed effects model for longitudinal QOL and a Cox model for survival. We use regression splines method to estimate the nonparametric curves and AIC to select knots. We assess the model performance through simulation to establish a novel modeling approach that could be used in future palliative care research trials. Application of our approach in a recently completed palliative care clinical trial is also presented.     

Assessment of quality of life in clinical trials.

This paper is intended as an overview of developments in the assessment of quality of life (QOL) in clinical trials over the last decade from the viewpoint of clinical biostatistics. In the first part we deal with aspects of obtaining adequate measurements of quality of life. A literature survey shows that a large number of quite heterogeneous measurement approaches for use in clinical trials exist, a substantial percentage of which cannot be regarded as sufficient for their actual measuring purpose. In the second part we review statistical methods applied to and adapted for the analysis of QOL data. Underlying the analysis should be the assumption of QOL as a stochastic process. Applied analysis procedures are again investigated in a literature survey. Finally, critical conclusions are outlined and suggestions for further research are given.     

Social impact of preventive HIV vaccine clinical trial participation: a model of prevention, assessment and intervention

Preventive HIV vaccine trial participants may experience problems related to trial participation, including difficulties with personal relationships, employment, education, health care, housing, health insurance, disability insurance, life insurance, travel or immigration. During the 19 years that the U.S.-based National Institute of Allergy and Infectious Diseases (NIAID) has conducted preventive HIV vaccine trials, we have developed a model to prevent and resolve social impact related to study participation and assist study participants who report such events. Key elements of the model include: informing potential volunteers of risks prior to enrollment; standardizing data collection methods on social impact events; reviewing and following-up on reported social impact events; assisting participants, including provision of free HIV testing to differentiate HIV infection from vaccine-induced HIV antibody; implementing broad-based and targeted community education programs for achieving community support; communicating with scientific and health care communities; and working with government agencies, non-government agencies and industry on mechanisms to address SI. This approach, established in collaboration with NIAID-funded clinical trial groups, serves as a model for prevention, assessment, monitoring, and intervention for social impact related to preventive HIV vaccine clinical trial participation. Although further research is necessary, this model could be adapted for use in different clinical trials.     

An exploratory study of frequent pain measurement in a cancer clinical trial

The ideal methodology for quality of life (QOL) measurement in cancer clinical trials matches the evaluation to the anticipated outcomes, thereby increasing the likelihood that clinically relevant changes are captured. The present study explored the importance of such methodological tailoring in a phase II trial of paclitaxel and recombinant human granulocyte-colony stimulating factor (rhG-CSF) for metastatic breast cancer. Prior to the trial, clinical observation suggested that frequent short-lived episodes of pain might occur during this treatment regimen. Twenty-one patients provided longitudinal data for at least three cycles of chemotherapy. To assess transient pain, aroutine QOL assessment at baseline and every third cycle was supplemented with pain measurements twice weekly. The interval assessment included a multidimensional QOL instrument (Functional Living Index-Cancer) and measures of psychological state (Rand Mental Health Inventory), symptom distress (Memorial Symptom Assessment Scale), and performance status (Karnofsky Performance Status Score). The frequent pain measurements were acquired using visual analogue and categorical scales for pain intensity (Memorial Pain Assessment Card). From baseline to the end of cycle three, global pain scores declined and the results on other QOL measures were variable. The data obtained using these measures did not reveal the existence of episodic pains. In contrast, the twice weekly pain measurements clearly demonstrated transient severe pains in approximately half the patients. These data highlight the importance of specific measurement of troubling symptoms or other relevant QOL concerns at clinically appropriate intervals during the routine QOL assessment of clinical trials. The additional burden involved in these assessments is warranted if the information derived is highly relevant, would not be adequately captured otherwise and could improve therapy.     

Menopause research: the Korpilampi workshop

A workshop on menopause research focused on three topics: (1) problems and issues in the definition of menopausal status: (2) problems and issues in cross-cultural research: (3) the contributions which research in the behavioural sciences can make to clinical research and practice. Among the conclusions reached by the workshop was the recommendation that researchers should adopt a standard definition of menopause based on the cessation on menses. Yet, while standard definitions are essential to scientific comparison, it is also important to determine how women decide on their own status, particularly when working cross-culturally.     

Training Community Health Workers About Cancer Clinical Trials

Innovative projects to reduce disparities in cancer treatment and research include partnerships between academic and community cancer centers, patient navigation programs and strategies to promote community awareness, education and engagement. A 4 h training program about cancer clinical trials was developed through a needs assessment and in collaboration with community health workers who served as consultants and a larger advisory board comprised of community health workers, educators and clinical trialists. This program was delivered first as a collaboration between a phsycian who is experienced in the conduct of clinical research and two community health workers, and subsequently by the community health workers alone. We report on four workshops attended by a total of 61 community health workers recruited from Boston-area hospitals, community health centers and outreach programs. Support for and knowledge of clinical trials was measured in a pretest and post-test, which also included a satisfaction rating. Participants had a range of prior experience with clinical trials in the context of their personal and professional experience. Mean accuracy of knowledge about clinical trials increased from 72 to 84%, support for clinical trials improved considerably, and satisfaction with the training experience was high. Knowledge gaps and low levels of support for cancer clinical trials among community health workers can be improved with a short training program delivered by other community health workers. Further research is needed to identify the impact of this training on accrual to cancer clinical trials.     

Joint modeling quality of life and survival using a terminal decline model in palliative care studies

Palliative medicine is a relatively new specialty that focuses on preventing and relieving the suffering of patients facing life‐threatening illness. For cancer patients, clinical trials have been carried out to compare concurrent palliative care with usual cancer care in terms of longitudinal measurements of quality of life (QOL) until death, and overall survival is usually treated as a secondary endpoint. It is known that QOL of patients with advanced cancer decreases as death approaches; however, in previous clinical trials, this association has generally not been taken into account when inferences about the effect of an intervention on QOL or survival have been made. We developed a new joint modeling approach, a terminal decline model, to study the trajectory of repeated measurements and survival in a recently completed palliative care study. This approach takes the association of survival and QOL into account by modeling QOL retrospectively from death. For those patients whose death times are censored, marginal likelihood is used to incorporate them into the analysis. Our approach has two submodels: a piecewise linear random intercept model with serial correlation and measurement error for the retrospective trajectory of QOL and a piecewise exponential model for the survival distribution. Maximum likelihood estimators of the parameters are obtained by maximizing the closed‐form expression of log‐likelihood function. An explicit expression of quality‐adjusted life years can also be derived from our approach. We present a detailed data analysis of our previously reported palliative care randomized clinical trial. Copyright © 2012 John Wiley & Sons, Ltd.     

Workshop report: environmental exposures and cancer prevention

The Workshop on Environmental Exposures and Cancer was held by Cancer Care Ontario (CCO) 25-26 April 2001. An expert panel convened to achieve consensus on a list of important environmental exposures, priority environmental exposures in Ontario, and recommendations for CCO in the areas of surveillance, research, and prevention activities to address these environmental exposures. Panel members developed a working definition of environmental exposure and criteria to prioritize the identified exposures. The process followed in the workshop provided CCO with important direction for its surveillance, research, and prevention activities to address environmental exposures and cancer. It is hoped that the environmental exposures and the opportunities identified through this workshop process will guide policy makers, program personnel, and researchers interested in and struggling with the challenges associated with surveillance, research, and prevention of environmental exposures.     

Quality-of-life concerns of African American breast cancer survivors within rural North Carolina: blending the techniques of photovoice and grounded theory

Social norms imposing a prevailing silence around breast cancer in rural African American communities have made it difficult for survivors to express their quality-of-life (QOL) concerns. In this article, the authors describe how they blended the photovoice method (providing participants with cameras so they can record, discuss, and relate the realities of their lives) with grounded theory techniques to assist 13 African American breast cancer survivors from rural eastern North Carolina in (a) exploring how they perceive and address their QOL within their own social context and (b) developing a conceptual framework of survivorship QOL. The framework that emerged reveals that three social forces (racism, stigmas regarding cancer, and cultural expectations of African American women) drive four QOL concerns (seeking safe sources of support, adjusting to the role of cancer survivor, feeling comfortable about the future, and serving as role models) and that survivors address these concerns by relying on spiritual faith and devising strategies to maintain social standing.     

Quality of life assessment and reporting in randomized controlled trials: a study of literature published from Japan

Background  

Standardization of quality of life (QOL) assessment and reporting in clinical trials is an imperative issue. While English-speaking countries have led this movement in standardization, there persists to be a limited amount of information from non-English-speaking including Japan. In this study, we bibliographically analyze the reporting of randomized controlled trials (RCT) conducted in Japan that used a QOL instrument.     

Individually different "weights" of quality of life assessment in patients with advanced nonsmall-cell lung cancer

BACKGROUND AND OBJECTIVE: The structure of quality of life (QOL) assessment was investigated by estimating subject-specific as well as population-averaged "weights" for four domains (functional, physical, mental, and psychosocial) relative to global QOL. METHODS: Among 583 eligible patients with advanced nonsmall-cell lung cancer in two phase III trials, 377 completed QOL questionnaires at baseline, and during treatment. A random coefficients model was applied, using the global QOL score and scores for the four domains as response and explanatory variables, respectively. RESULTS: A large diversity in subject-specific weights was found for the physical and psychosocial domains during treatment and for the psychosocial and functional domains after treatment. The population-averaged weights of all domains were significant during treatment (especially the physical domain), as well as after treatment (except the functional domain). CONCLUSION: Thus, all four domains were associated with global QOL, and the associations varied among individual patients as well as among the domains.     

Approaches to the analysis of quality of life data: experiences gained from a Medical Research Council Lung Cancer Working Party palliative chemotherapy trial

Standardization in the choice of quality of life (QOL) instruments and their application in randomised clinical trials have been advocated and generally accepted. However, there is now an urgent need to address the problems relating to the analysis and presentation of the data thus generated. There are intrinsic difficulties associated with QOL data, namely its multidimensional nature, attrition and missing data, and there is no consensus as to how these problems should be dealt with. This paper therefore considers there problems using interim data from a large Medical Research Council randomised trial in patients with small cell lung cancer and a poor prognosis, in which attrition and compliance are major concerns. Three possible approaches to the analysis of these data, which use different subsets of patients, are examined in detail. The strengths and weaknesses of these three methods are discussed, and examples of their use in the literature are given and compared with other reported approaches. The need for a standard definition of compliance is also emphasised, and a method of presentation suggested. The best current advice is that QOL data should be analysed in a number of different ways, and conclusions reached only when consistency is seen.P. Hopwood is supported by the Cancer Research Campaingn.This paper is based on a presentation given by one of the authors (PH) at the British Psychosocial Oncology Group Conference in December 1992.This paper is given on behalf of the MRC Lung Cancer Working Party whose members are Bleehen N. M., Bolger J. J., Clark P. I., Girling D. J., Hasleton P. S., Hopwood P., Macbeth F. R., Machin D., Moghissi K., Saunders M. I., Stephens R. J., Thatcher N. (Chairman) and White R. J.     

Increasing Primary Care Physician Support for and Promotion of Cancer Clinical Trials

Only 2.5%–3% of adult cancer patients participate in cancer clinical trials, yet about 20% of cancer patients are medically eligible to participate. Research suggests that the primary care provider (PCP) can influence a patient''s awareness of, and potentially, his or her decision to consider a clinical trial. To address low cancer clinical trial accrual rates, ‘Imi Hale Native Hawaiian Cancer Network partnered with The Queen''s Cancer Center to provide and evaluate education on clinical trials to Hawai‘i PCPs. The educational materials were developed from a national curriculum and tailored to local audiences. Objectives of the curriculum were to educate PCPs about common myths (attitudinal barriers) around clinical trials and suggest ways that PCPs can introduce the concept of clinical trials to their patients with cancer or suspicion of cancer. The curriculum was tested on 128 PCPs in 2012. Knowledge of the PCP''s role and their willingness to mention clinical trials were measured through a post-test immediately following the presentation, which 74 (58%) PCPs completed. The post-test results suggested an increase in awareness among PCPs of their potential role in cancer clinical trial accrual, and an increase in PCP willingness to mention clinical trials to their patients with suspicion of cancer or diagnosed with cancer. Although findings suggest that this intervention is useful in increasing PCP receptivity to promoting cancer clinical trials, more research is needed to test if increased willingness results in increased accrual of cancer patients into clinical trials in Hawai‘i.     

The World Health Organization's WHOQOL-BREF quality of life assessment: Psychometric properties and results of the international field trial. A Report from the WHOQOL Group

Quality of life (QOL) assessments that are easily administered and which do not impose a great burden on the respondent are needed for use in large epidemiological surveys, clinical settings and clinical trials. Using data from the WHOQOL-BREF field trials, the objectives of this work are to examine the performance of the WHOQOL-BREF as an integrated instrument, and to test its main psychometric properties. The WHOQOL-BREF is a 26-item version of the WHOQOL-100 assessment. Its psychometric properties were analysed using cross-sectional data obtained from a survey of adults carried out in 23 countries (n = 11,830). Sick and well respondents were sampled from the general population, as well as from hospital, rehabilitation and primary care settings, serving patients with physical and mental disorders and with respect to quotas of important socio-demographic variables. The WHOQOL-BREF self-assessment was completed, together with socio-demographic and health status questions. Analyses of internal consistency, item-total correlations, discriminant validity and construct validity through confirmatory factor analysis, indicate that the WHOQOL-BREF has good to excellent psychometric properties of reliability and performs well in preliminary tests of validity. These results indicate that overall, the WHOQOL-BREF is a sound, cross-culturally valid assessment of QOL, as reflected by its four domains: physical, psychological, social and environment.